Understanding And Preventing Secondary Degeneration Following CNS Injury
Funder
National Health and Medical Research Council
Funding Amount
$409,147.00
Summary
After neurotrauma, tissue escaping initial injury undergoes secondary degeneration; tissue loss spreads, function worsens. In the complex brain and spinal cord it is difficult to distinguish vulnerable tissue. Using the visual system as a model I will precisely identify cells and processes of secondary degeneration, determine if vulnerable tissue can be rescued by drugs stopping toxic calcium influx and if rescued circuits work properly. The work has implications for neurotrauma and glaucoma.
I will use non-invasive brain stimulation to study the operation of the corticospinal pathway in humans while they perform tasks requiring precise control of fingers and thumb. This pathway from brain to spinal cord is important for independent finger movements, and these experiments will provide insight into the cortical mechanisms by which independent finger movements are produced. I will also investigate relationships between patterns of corticospinal activation (which I have shown differ bet ....I will use non-invasive brain stimulation to study the operation of the corticospinal pathway in humans while they perform tasks requiring precise control of fingers and thumb. This pathway from brain to spinal cord is important for independent finger movements, and these experiments will provide insight into the cortical mechanisms by which independent finger movements are produced. I will also investigate relationships between patterns of corticospinal activation (which I have shown differ between subjects and hands) and digital dexterity. While it seems reasonable to assume that digital dexterity is dependent on the operation of the corticospinal system, the relationship is obscure, even at a gross level. Digital dexterity can vary considerably between subjects, and even between hands in the same subject. Are people more skilled with their hands because they are better able to engage the corticospinal system in control of the digits? The present study will address this fundamental question. The brain stimulation techniques that I will use are the only techniques presently available which can answer these questions in humans. This information will assist us to understand how normal subjects perform skilled tasks with their hands, as well as helping us to understand how damage to the nervous system (e.g., stroke, multiple sclerosis, Parkinson's disease) produces deficits in movement control. The information gained may suggest training regimes for skill acquisition in normal subjects, and to promote recovery of function in patients with neurological damage or disease.Read moreRead less
Representation Of Spatial Coordinate Systems Within Posterior Parietal Cortex And Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$43,759.00
Summary
To accurately reach for an object or walk from one room to another, our brains need to be able to locate objects around us and detect obstacles in our path. Our amazing ability to make an accurate eye movement directly towards an object such as a cup of tea and move our hand smoothly and directly to the cup is something we all take for granted. However, this ability requires enormous computational complexity which our brains have evolved to handle with ease. We plan to determine the parts of the ....To accurately reach for an object or walk from one room to another, our brains need to be able to locate objects around us and detect obstacles in our path. Our amazing ability to make an accurate eye movement directly towards an object such as a cup of tea and move our hand smoothly and directly to the cup is something we all take for granted. However, this ability requires enormous computational complexity which our brains have evolved to handle with ease. We plan to determine the parts of the brain that perform these computations by using a relatively new technique called functional magnetic resonance imaging or fMRI. This is a non-invasive technique that requires a person to lie in an MRI scanner and perform simple eye movement tasks while the scanner takes images of the brain. With this technology we are able to determine which regions of the brain are most active during the performance of each task, thereby giving us an insight into how the brain works. An area of the brain called the parietal lobe is thought to be involved in the localization of objects, such as reaching for a cup of tea. We will study this area using fMRI to determine how a map of space is represented within the parietal lobe. This region of the brain communicates with another region, the hippocampus which is thought to be involved in navigation, such as walking about the house or driving in the city. Functional MRI will be used to study the hippocampus of our subjects while they perform simple navigational tasks through a maze which is simulated on a computer screen. This will reveal the role hippocampus plays in navigation and the relationship between the parietal lobe and hippocampus. We hope that the greater understanding of hippocampus that will arise from this study will enable us to devise a robust method for imaging hippocampal function with fMRI. We expect that these techniques will aid in the diagnosis of hippocampal abnormalities in patients with temporal lobe epilepsy.Read moreRead less
Neural Coding Of A Cue To Auditory Space, In Noisy Environments
Funder
National Health and Medical Research Council
Funding Amount
$180,160.00
Summary
GENERAL BACKGROUND : Our ability to determine where a sound is coming from (localization ability) is severely disrupted when the environment is noisy. This affects our abilities at many ordinary tasks, such as keeping up a conversation in a noisy background, and also in other critical tasks (eg., in following warning signals in a noisy factory environment). In people who have some hearing loss, even if only partial deafness, localization ability is disrupted even when there is no noise in the ba ....GENERAL BACKGROUND : Our ability to determine where a sound is coming from (localization ability) is severely disrupted when the environment is noisy. This affects our abilities at many ordinary tasks, such as keeping up a conversation in a noisy background, and also in other critical tasks (eg., in following warning signals in a noisy factory environment). In people who have some hearing loss, even if only partial deafness, localization ability is disrupted even when there is no noise in the background, and is even more severely disrupted when the environment is noisy. SCIENTIFIC BACKGROUND : Our localization ability depends on the way neurons in the brain code the position of a source of sound we wish to detect. From studies in animals we know a lot about the way in which neurons do this coding in silence. However, we know almost nothing about how this coding is affected by a noisy background. Further, we know absolutely nothing about how this coding, whether in silence or when there is noise, is affected when there is also a hearing loss. SIGNIFICANCE : If we are to understand the effects of hearing losses on coding of the location of a sound signal we need to know first how noise affects the coding in cases of normal hearing. This project aims to gain that information. I will then extend this to studying the detailed basis of these effects, ie., exactly what mechanisms are affected in the neurons. Then I will determine how noise from different positions affects the coding of signal sounds at differnt positions. These data will provide us the essential base from which we can, later, go on to study how noise affects coding by neurons of the location of a signal. I plan to increase the value of the current study by developing, from the data gained in the studies in animals, computer-based models that will allow us to predict how coding of sound signal location is affected by hearing loss, and how this is exacerbated by noisy environments.Read moreRead less
I am a clinical scientist translating basic science findings into clinical science questions and answers that impart better understanding and management of pain and painful disease.
Neural Plasticity Following Lesions Of The Central Nervous System In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$523,487.00
Summary
The brain and nervous system can adapt to injury and disease. The compensatory changes underlying this plasticity can ameliorate disability. This project will investigate the underlying mechanisms in patients with multiple sclerosis, by examining changes in the properties of nerve fibres in the peripheral nerve. The rationale for the project is that the properties of peripheral nerve fibres can reflect, at least in part, the properties of their cell bodies within the spinal cord.
Characterization Ol A Novel Covalently Cross -linked Abeta Peptide Dimer And Its Role In Alzheimers Disease.
Funder
National Health and Medical Research Council
Funding Amount
$553,236.00
Summary
Currently there are limited therapeutic treatments and no cure for Alzheimer's disease (AD). The key protein causing AD is called Abeta. Abeta peptides form dityrosine cross-linked dimers (when 2 peptides join together) and this is thought to be responsible for killing brain cells in AD. Therefore, this proposal will determine the role of Abeta dimers in relation to killing brain cells and the progression of AD through analysis of their biological and biochemical properties.
The Effect Of Metals On Neurofibrillary Tangle Formation
Funder
National Health and Medical Research Council
Funding Amount
$333,313.00
Summary
The majority of studies into Alzheimer's disease (AD) have focussed on two brain lesions- the plaque and neurofibrillary tangle (NFT), which are believed to have a causative role in AD. Our lab has made several seminal discoveries about the role that metals play in the development of plaques. We are now extending this work to evaluate the role of metals in NFT formation. These studies will provide insight into the formation and possible treatments for this primary brain lesion in AD.
An Analysis Of A Model Of Movement Disorder Lacking D1R Positive Neurons.
Funder
National Health and Medical Research Council
Funding Amount
$346,446.00
Summary
The experiments outlined in this project proposal are aimed at further characterizing a genetically engineered mouse the generation of which was originally funded by the Australian NH and MRC. The mutant mouse suffers from the loss of brain cells in a part of the brain called the striatum. The mouse model will allow us to understand how damage to brain structures cause disabling human neurodegenerative diseases such as Parkinsonism and Huntington's disease. The mouse model is unique as the mice ....The experiments outlined in this project proposal are aimed at further characterizing a genetically engineered mouse the generation of which was originally funded by the Australian NH and MRC. The mutant mouse suffers from the loss of brain cells in a part of the brain called the striatum. The mouse model will allow us to understand how damage to brain structures cause disabling human neurodegenerative diseases such as Parkinsonism and Huntington's disease. The mouse model is unique as the mice suffer from the same type of movement abnormalities which afflict individuals with this spectrum of neurological illnesses. We will look at both structural changes in the brain as well as brain function as defined by the behavioural responses of the damaged brain to drug administration. The experiments also focus on the ultimate correction of the neurological deficits by transplantation of purified nerve cell progenitor cells.Read moreRead less